ABSTRACT
The roles of cGMP, prostaglandins, the entry of extracellular Ca2+ through slow channels, endothelium and V1 receptors in the negative inotropic, chronotropic and coronary vasoconstrictor responses to arginine vasopressin (AVP) have been investigated in isolated perfused rat hearts. The bolus injection of 5 x 10(-5) M AVP produced a significant decrease in contractile force, heart rate and coronary flow. AVP also significantly decreased contractile force, heart rate and coronary flow in hearts pretreated with an inhibitor of soluble guanylate cyclase methylene blue (10(-6) M), an effective drug for removing endothelium saponin (500 micrograms/ml), an inhibitor of cyclooxygenase indomethacin (10(-5) M) or a calcium channel antagonist verapamil (5 x 10(-7) M). The potent V1 receptor antagonist [Deamino-Pen1, Val4, D-Arg8]-vasopressin (9 x 10(-5) M) did not alter effects of AVP but the very potent V1 receptor antagonist [beta-Mercapto-beta, beta-cyclopentamethylene-propionyl1, O-Me-Tyr2, Arg8]-vasopressin (8 x 10(-5) M) abolished these effects. Our results suggest that AVP produces negative inotropic, chronotropic and coronary vasoconstrictor effects in isolated perfused rat hearts. cGMP, prostaglandin release and Ca2+ entry does not involve in the effects of AVP. These effects are endothelium independent and mediated by V1 receptors. The use of V1 receptor antagonist [beta-mercapto-beta, beta-cyclopentamethylene-propionyl1, O-Me-Tyr2, Arg8]-vasopressin may be beneficial for preventing the negative inotropy, chronotropy and coronary vasoconstriction induced by AVP.